title: Altered enteric microbiota ecology in interleukin 10-deficient mice during development and progression of intestinal inflammation.
abstract: Inflammatory bowel diseases (IBD) result from dysregulated immune responses toward microbial and perhaps other luminal antigens in a genetically susceptible host, and are associated with altered composition and diversity of the intestinal microbiota. The interleukin 10-deficient (IL-10 (-/-) ) mouse has been widely used to model human IBD; however the specific alterations that occur in the intestinal microbiota of this mouse model during the onset of colonic inflammation have not yet been defined. The aim of our study was to define the changes in diversity and composition that occur in the intestinal microbiota of IL-10 (-/-) mice during the onset and progression of colonic inflammation. We used high throughput sequencing of the 16S rRNA gene to characterize the diversity and composition of formerly germ-free, wild-type and IL-10 (-/-) mice associated with the same intestinal microbiota over time. Following two weeks of colonization with a specific pathogen-free (SPF) microbiota we observed a significant increase in the diversity and richness of the intestinal microbiota of wild-type mice. In contrast, a progressive decrease in diversity and richness was observed at three and four weeks in IL-10 (-/-) mice. This decrease in diversity and richness was mirrored by an increase in Proteobacteria and Escherichia coli in IL-10 (-/-) mice. An increase in E. coli was also observed in conventionally raised IL-10 (-/-) mice at the point of colonic inflammation. Our data reports the sequential changes in diversity and composition of the intestinal microbiota in an immune-mediated mouse model that may help provide insights into the primary vs. secondary role of dysbiosis in human IBD patients.
authors.affiliation: Division of Gastroenterology and Hepatology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, NC, USA.
authors.forename: Nitsan
authors.initials: N
authors.lastname: Maharshak
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Packey
authors.forename: Melissa
authors.initials: M
authors.lastname: Ellermann
authors.forename: Sayeed
authors.initials: S
authors.lastname: Manick
authors.forename: Jennica P
authors.initials: JP
authors.lastname: Siddle
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Huh
authors.forename: Scott
authors.initials: S
authors.lastname: Plevy
authors.forename: R Balfour
authors.initials: RB
authors.lastname: Sartor
authors.forename: Ian M
authors.initials: IM
authors.lastname: Carroll
mesh_terms: D000818:Animals; D058448:Biota; D004195:Disease Models, Animal; D041981:Gastrointestinal Tract / Q000382:microbiology*; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000382:microbiology*; D016753:Interleukin-10 / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10
keywords: Interleukin 10-deficient mouse; inflammatory bowel diseases; intestinal microbiota